Helicobacter pylori activates μ‐calpain to cleave E‐cadherin in epithelial monolayers
Bibliographic record
Abstract
H.pylori (Hp) is a risk factor for gastritis, gastric ulcers, and adenocarcinoma. The ability of Hp to disrupt epithelial intercellular adhesion may influence disease severity. Disruption of adherens junction (AJ) protein E‐cadherin has a well‐established role in carcinogenesis. Calpain family proteases are upregulated in several types of adenocarcinoma and can cleave E‐cadherin to a functionally‐impaired 100kDa form. AIMS: 1) to determine the effects of Hp on calpains, 2) to assess the role of calpains in Hp‐induced AJ alterations. RESULTS: Epithelial (SCBN) monolayers challenged with Hp strain SS1 or 60190 for 24h had increased calpain activity and elevated levels of the cleaved form of the calpain substrate α‐spectrin, as determined by activity assay and immunoblotting. Immunoblotting for the μ and m calpain isoforms revealed that μ, but not m, calpain is activated in response to Hp. Immunostaining and western blotting of subcellular fractions revealed loss of membrane‐associated E‐cadherin and increased cytosolic E‐cadherin. Western blotting of whole cell lysates demonstrated that Hp challenge induced cleavage of the 120kDa full‐length E‐cadherin to a 100kDa form. Calpain inhibition prevented these junctional defects. CONCLUSION: Carcinogenic Hp induces isoform‐specific calpain activation which results in E‐cadherin truncation in non‐tumorigenic epithelial cells. This work is funded by CIHR.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".